Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model.
As previously published, after aerosol infection with Mycobacterium tuberculosis H37Rv, New Zealand white rabbits established infection with active bacillary replication, but later contained disease to a paucibacillary state through an effective adaptive response consistent with latency. Despite the heterogeneity among outbred rabbits, the resistant response was uniform. Immunosuppression resulted in reactivation with increased lung bacillary burden. Using this rabbit model, we isolated bacillary RNA from infected rabbit lungs and assessed transcriptional profiles of bacillary genes using RT-PCR to examine genes differentially regulated during active replication, persistence, steroid-induced reactivation, and post-steroid immune reconstitution. Genes involved in hypoxia response (fdxA), resuscitation promoting factors (rpfB), and DNA repair pathways (Rv2191) may be important in bacillary persistence. Further investigation into these gene pathways is warranted.
Kesavan
Anup K
AK
Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD 21205, USA.
Brooks
Megan
M
Tufariello
JoAnn
J
Chan
John
J
Manabe
Yukari C
YC
D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology*; D023421:Models, Animal; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology
D007166:Immunosuppressive Agents; D003907:Dexamethasone